Anti-CD3 monoclonal antibody(University of Cambridge/University of Oxford)

Adoptive cell therapy (ACT) has revolutionized the treatment of patients with cancer. The success of ACT depends largely on transferred T cell status, particularly their less-differentiated state with stem cell-like properties, which enhances ACT effectiveness. Stem cell-like memory T (T_SCM) cells exhibit continuous self-renewal and multilineage differentiation similar to pluripotent stem cells. T_SCM cells are promising candidates for cancer immunotherapies, whereas maintenance of a more stem-cell-like state before transfer is challenging. Here, we established a highly efficient protocol for generating CD8⁺ T_SCM cells from peripheral blood mononuclear cells (PBMCs). The process involved activating PBMCs using anti-CD3 monoclonal antibody and RetroNectin, followed by a transient-resting culture period (24 h) and subsequent long-term expansion in vitro with interlukien-2. We report that this transient-resting culture after activation preserves CD8⁺ T cells in a stem memory phenotype (CD95⁺ CD45RA⁺ CCR7⁺) compared to the conventional culture method. Further, this approach reduces the expression of T cell immunoglobulin mucin-3, an exhaustion marker, and increases the expression of T cell factor-1, a master regulator of stemness even after long-term culture compared to the conventional culture method. In conclusion, our study presents a simplified and cost-effective method for generating and expanding CD8⁺ T_SCM cells ex vivo. This approach streamlines the optimization of cancer immunotherapy using ACT.

Type 1 diabetes (T1D) is characterized by the progressive destruction of insulin-producing beta cells in the pancreas. Despite improvements in insulin monitoring techniques, there remains no cure for T1D. Individuals with T1D require lifelong insulin therapy and some develop life-threatening complications. T1D is a complex, multifactorial, autoimmune condition. Understanding why people get T1D and how it progresses has advanced our knowledge of the disease and led to the discovery of specific targets that can be therapeutically manipulated to halt or reverse the course of T1D. Scientists investigating the potential of immunotherapy treatment for the treatment have recently had some encouraging results. Teplizumab, an anti-CD3 monoclonal antibody that has been approved by the FDA, delays the onset of clinical T1D in patients ≥ 8 years of age with preclinical T1D and improves beta cell function. Therapies targeting beta cell health, vitality, and function are now thought to be an essential component of successful combination therapy for T1D. The idea that the beta cells themselves may influence their own destruction during the development of T1D is a notion that has recently been gaining acceptance in the field. Researchers have recently made remarkable strides in beta cell replacement therapy and beta cell regeneration techniques. This review offers a detailed exploration of the pathophysiological mechanisms of T1D. It discusses the intricate interplay of factors leading to T1D development and the innovative approaches being explored to discover new treatments and a cure for the millions of people living with T1D worldwide.